Video‐EEG evidence of lateralized clinical features in primary generalized epilepsy with tonic‐clonic seizures

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Abstract
Background Whether cortical or subcortical structures, specifically the thalamus, play the dominant role in generating primary generalized seizures has been the subject of long debate. Most experimental data implicate a hyperexcitable cortical generator of spike-and-wave activity, with the thalamus quickly recruited to sustain the generalized oscillations through a reverberating thalamocortical network. However, there is little clinical evidence to support the cortical generator hypothesis. We present video-EEG recordings of generalized tonic-clonic seizures in three patients with proven primary generalized epilepsy (PGE), all of whom showed a consistent pattern of lateralized seizure onset compatible with a focal frontal lobe generator. Methods Among 300 patients referred for video-EEG monitoring for intractable epilepsy, three were found to have PGE with tonic-clonic convulsions. All had a positive family history for epilepsy and no other epilepsy risk factors. Epilepsy onset was during adolescence (2/3) or childhood (1/3). Patients were taking 1-4 antiepileptic drugs (AEDs) at admission, none of which was valproic acid. Results Interictal EEG showed very active, bilaterally synchronous generalized spike-and-wave or polyspike-and-wave discharges between 2.5-4.5 Hz, maximal over the midfrontal structures symetrically in all patients. Ictal EEG showed generalized rhythmic activity without lateralization at seizure onset. Surprisingly, in all 6 recorded tonic-clonic seizures there was a sustained (10-15 seconds), stereotyped, clinical lateralization at onset, which took the form of a tonic “fencing posture” in one patient (two seizures) and forced head/eye/torso version in two patients (four seizures). Two patients became seizure-free shortly after switching to valproate monotherapy. One patient refused valproate but has improved more than 90 % with a change in AEDs to lamotrigine and phenobarbital (follow-up in all patients > 18 months). Conclusions Tonic-clonic seizures are presumed to be generalized from onset in patients with PGE. However, video-EEG monitoring in these patients is rarely performed and the actual clinical features of the seizures may be underappreciated. The demonstration of sustained lateralization at onset in our patients, with features clinically indistinguishable from focal onset frontal lobe seizures, is compatible with the hypothesis of a focal region of cortical hyperexcitability situated in the frontal lobes of some patients with PGE. Whether this cortical generator is autonomous or “triggered” by ascending, possibly normal, thalamocortical volleys is unresolved. [Published with video sequences].